Study of the Effects of the Organism on Monomethyl Fumarate (MMF) After the Administration of LAS41008

NCT02955693 | Completed Phase 1

• 3 other identifiers: M-41008-08PXL2306232016-002314-50
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how the organism affects MMF (metabolite of dimethyl fumarate \[DMF\]) after single oral dose administration of LAS41008 120 mg gastroresistant tablet and Fumaderm® 120 mg gastro-resistant tablet under fasting and fed conditions. The study also aims to assess the safety of the study treatments.

Conditions

Psoriasis

Keywords

Pharmacokinetics; Healthy volunteers; Monomethylfumarate; Dimethyl fumarate; Fumaderm®; Ethyl fumarate

Outcome Measures

Primary Outcomes (4)

• Area under the concentration-time curve from zero to time t (AUC(0-t)) of LAS41008 120 mg/Fumaderm® 120 mg

  t is the time of the last concentration measured

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• Cmax of LAS41008 120 mg/Fumaderm® 120 mg

  Maximum plasma concentration

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• tmax of LAS41008 120 mg/Fumaderm® 120 mg

  Time to reach maximum plasma concentration

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• tlag of LAS41008 120 mg/Fumaderm® 120 mg

  Lag time

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

Secondary Outcomes (5)

• Area under the concentration-time curve from zero to infinity (AUC) of LAS41008 120 mg/Fumaderm® 120 mg

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• Extrapolated part of AUC (%AUCext) of LAS41008 120 mg/Fumaderm® 120 mg

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• t1/2 of LAS41008 120 mg/Fumaderm® 120 mg

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• Formation clearance of a drug to a metabolite (CL/f) of LAS41008 120 mg/Fumaderm® 120 mg

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

• Vz/f of LAS41008 120 mg/Fumaderm® 120 mg

  Within 1 hour pre-dose and post-dose at: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 13, 14, 16 and 24 hours (29 blood samples in each period)

Other Outcomes (8)

• Blood pressure

  at Visit 1 (screening), 1 hour pre-dose and approximately at the same time on Day 2 of each period

• Pulse rate

  at Visit 1 (screening), 1 hour pre-dose and approximately at the same time on Day 2 of each period

• Oral body temperature

  at Visit 1 (screening) and pre-dose on Day 1 of each period

Study Arms (4)

Sequence A (n=8)

OTHER

Fumaderm® 120 mg fed (Period 1) - LAS41008 120 mg fasting (Period 2) -Fumaderm® 120 mg fasting (Period 3) - LAS41008 120 mg fed (Period 4)

Drug: LAS41008 120 mg / Fumaderm® 120 mg

Sequence B (n=8)

OTHER

LAS41008 120 mg fasting (Period 1) - LAS41008 120 mg fed (Period 2) - Fumaderm® 120 mg fed (Period 3) - Fumaderm® 120 mg fasting (Period 4)

Drug: LAS41008 120 mg / Fumaderm® 120 mg

Sequence C (n=8)

OTHER

Fumaderm® 120 mg fasting (Period 1) - Fumaderm® 120 mg fed (Period 2) - LAS41008 120 mg fed (Period 3) - LAS41008 120 mg fasting (Period 4)

Drug: LAS41008 120 mg / Fumaderm® 120 mg

Sequence D (n=8)

OTHER

LAS41008 120 mg fed (Period 1) - Fumaderm® 120 mg fasting (Period 2) - LAS41008 120 mg fasting (Period 3) - Fumaderm® 120 mg fed (Period 4)

Drug: LAS41008 120 mg / Fumaderm® 120 mg

Interventions

LAS41008 120 mg / Fumaderm® 120 mg DRUG

Single dose of LAS41008 120 mg or Fumaderm® 120 mg in each Period

Also known as: LAS41008: DMF / Fumaderm®: DMF + Ca, Mg and Zn salts of EHF

Sequence A (n=8); Sequence B (n=8); Sequence C (n=8); Sequence D (n=8)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who are able to understand and follow instructions during the study as determined by the Investigator.
• Signed and dated informed consent.
• Men and women of any ethnic origin between 18 and 55 years of age (inclusive, at the time of Screening) in general good physical health as determined by medical and surgical history, physical examination, ECG, vital signs, and clinical laboratory tests (including clinically significant changes in laboratory test).
• Weight within the normal range according to accepted values for the body mass index (BMI) within 18.0 to 29.0 kg/m2 (inclusive, at the time of Screening), and a body weight of at least 50 kg.
• Normal blood pressure (Systolic Blood Pressure ≥ 90, ≤ 139 mmHg; Diastolic Blood Pressure ≥ 55, ≤ 89 mmHg) measured after at least 5 minutes rest in supine position.
• A pulse rate of ≥ 45 and ≤ 99 beats per minute measured after at least 5 minutes rest in supine position.
• ECG recording, in triplicate, taken at least 1 minute apart; after at least 5 minutes of rest in a supine position without clinically significant abnormalities.

You may not qualify if:

• Subject who has received live-attenuated vaccine(s) within 4 weeks of Day 1 or plan to receive a vaccination during the study until 6 months after the last dose of study medication.
• More than moderate smoker (\> 10 cigarettes/day).
• Demonstrating excess in xanthine consumption (more than five cups of coffee or equivalent per day).
• More than moderate alcohol consumption (subjects will be advised to consume no more than 2 units of alcohol per day and completely abstain from 72 hours prior to any visit (1 unit is equal to approximately 10 g of pure alcohol \[250 mL\] of beer \[5%\], 1 small glass \[100 mL\] of wine \[12%\] or 35 mL of spirits \[35%\]).
• Any history of alcohol or drug abuse or excessive intake of alcohol, as judged by the Investigator.
• Any history of drug hypersensitivity, asthma (with the exception of childhood asthma), urticaria or other severe allergic diathesis as well as active hay fever.
• Any history of hypersensitivity or lack of tolerability to the ingredients of the investigational medicinal product (IMP).
• Having febrile or infectious illness within at least 7 days prior to the Visit 1 (Screening) and Day -1 of Period 1.
• Any presence of acute or chronic liver or renal diseases.
• Any history or presence of gastrointestinal disease or problems including chronic gastritis, peptic ulcers, diarrhoea, or inflammatory bowel disease.
• Any history of clinically significant chronic or recurrent metabolic, pulmonary, neurological (especially history of epileptic seizures), endocrinological, immunological, psychiatric or cardiovascular disease, myopathies, and bleeding tendency.
• Subjects who have ever received immunosuppressant treatment (excluding topical or oral steroids taken 1 and 5 years before Visit 1 \[Screening\] respectively).
• Any history of frequent headache or migraine.
• Any history of malignancies (excluding basal skin cell cancer), as judged by the Investigator.
• Non-vasectomised man not using barrier contraception during the study.

Sponsors & Collaborators

• Almirall, S.A.: lead

Study Sites (1)

Almirall Investigational Site #1

London, Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Psoriasis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Wolf-Godehard Ocker, MD

  Almirall Hermal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: November 4, 2016
• Study Start: September 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 22, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)